Prevalence of and Risk Factors for Post-COVID-19 Condition during Omicron BA.5-Dominant Wave, Japan.

The increased risk for post-COVID-19 condition after the Omicron-dominant wave remains unclear. This population-based study included 25,911 persons in Japan 20-69 years of age with confirmed SARS-CoV-2 infection enrolled in the established registry system during July-August 2022 and 25,911 age- and sex-matched noninfected controls who used a self-reported questionnaire in January-February 2023. We compared prevalence and age- and sex-adjusted odds ratios of persistent COVID-19 symptoms (lasting ≥2 months). We evaluated factors associated with post-COVID-19 condition by comparing cases with and without post-COVID-19 condition. We analyzed 14,710 (8,392 cases and 6,318 controls) of 18,183 respondents. Post-COVID-19 condition proportion among cases was 11.8%, higher by 6.3% than 5.5% persistent symptoms among controls. Female sex, underlying medical conditions, mild to moderate acute COVID-19, and vaccination were associated with post-COVID-19 condition. Approximately 12% had post-COVID-19 condition during the Omicron-dominant wave, indicating the need for longer follow-up.

Fecal Microbiota Transplantation for Sleep Disturbance in Post-acute COVID-19 Syndrome.

BACKGROUND & AIMS: Post-acute COVID-19 syndrome (PACS) is associated with sleep disturbance, but treatment options are limited. The etiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of fecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a nonrandomized, open-label prospective interventional study. METHODS: Between September 22, 2022, and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥8 and assigned them to the FMT group (FMT at weeks 0, 2, 4, and 8; n = 30) or the control group (n = 30). The primary outcome was clinical remission defined by an ISI of <8 at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7 scale, Epworth Sleepiness Scale, Multidimensional Fatigue Inventory, blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing. RESULTS: At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; P = .018). The FMT group showed a decrease in ISI score (P < .0001), Pittsburgh Sleep Quality Index (P < .0001), Generalized Anxiety Disorder-7 scale (P = .0019), Epworth Sleepiness Scale (P = .0057), and blood cortisol concentration (P = .035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. The gut microbiome profile resembled that of the donor in FMT responders but not in nonresponders at week 12. There was no serious adverse event. CONCLUSIONS: This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia, and further clinical trials are warranted. CLINICALTRIALS: gov, Number: NCT05556733.

Association of gut microbiota with the pathogenesis of SARS-CoV-2 Infection in people living with HIV.

BACKGROUND: People living with HIV (PLWH) with chronic inflammation may have an increasing risk for coronavirus disease 2019 (COVID-19) severity; however, the impact of their gut microbiota on COVID-19 is not fully elucidated. Here, we analyzed the temporal changes in the gut microbiota composition of hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (PLWH-CoV) and their correlation with COVID-19 severity. RESULT: The 16S rRNA analysis results using stool samples (along the timeline from disease onset) from 12 hospitalized PLWH-CoV, whose median CD4 + T cell count was 671 cells/µl, were compared to those of 19 healthy people and 25 PLWH. Bacterial diversity in PLWH-CoV is not significantly different from that of healthy people and SARS-CoV-2 non-infected PLWH, but a significant difference in the microbiota diversity was observed in the classification according to the disease severity. Immediately after the disease onset, remarkable changes were observed in the gut microbiota of PLWH-CoV, and the changing with a decrease in some short-chain fatty acid-producing bacteria and an increase in colitis-related pathobiont. In the second week after disease onset, relative amounts of specific bacteria distinguished between disease severity. One month after the disease onset, dysbiosis of the gut microbiota persisted, and the number of Enterobacteriaceae, mainly Escherichia-Shigella, which is potentially pathogenic, increased and were enriched in patients who developed post-acute sequelae of COVID-19 (PASC). CONCLUSION: The changes in the gut microbiota associated with SARS-CoV-2 infection observed in PLWH in this study indicated a persistent decrease in SCFA-producing bacteria and an intestinal environment with an increase in opportunistic pathogens associated with enteritis. This report demonstrates that the intestinal environment in PLWH tends to show delayed improvement even after COVID-19 recovery, and highlights the importance of the dysbiosis associated with SARS-CoV-2 infection as a potential factor in the COVID-19 severity and the PASC in PLWH.

Patient Experiences Navigating Care Coordination For Long COVID: A Qualitative Study.

BACKGROUND: Little is known about how to best evaluate, diagnose, and treat long COVID, which presents challenges for patients as they seek care. OBJECTIVE: Understand experiences of patients as they navigate care for long COVID. DESIGN: Qualitative study involving interviews with patients about topics related to seeking and receiving care for long COVID. PARTICIPANTS: Eligible patients were at least 18 years of age, spoke English, self-identified as functioning well prior to COVID infection, and reported long COVID symptoms continued to impact their lives at 3 months or more after a COVID infection. APPROACH: Patients were recruited from a post-COVID recovery clinic at an academic medical center from August to September 2022. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis. KEY RESULTS: Participants (n=21) reported experiences related to elements of care coordination: access to care, evaluation, treatment, and ongoing care concerns. Some patients noted access to care was facilitated by having providers that listened to and validated their symptoms; other patients reported feeling their access to care was hindered by providers who did not believe or understand their symptoms. Patients reported confusion around how to communicate their symptoms when being evaluated for long COVID, and they expressed frustration with receiving test results that were normal or diagnoses that were not directly attributed to long COVID. Patients acknowledged that clinicians are still learning how to treat long COVID, and they voiced appreciation for providers who are willing to try new treatment approaches. Patients expressed ongoing care concerns, including feeling there is nothing more that can be done, and questioned long-term impacts on their aging and life expectancy. CONCLUSIONS: Our findings shed light on challenges faced by patients with long COVID as they seek care. Healthcare systems and providers should consider these challenges when developing strategies to improve care coordination for patients with long COVID.

Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment.

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients. To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3 T-MRI scans and signature inflammatory markers in n = 120 participants comprising healthy never-infected controls (n = 30), healthy COVID-19 survivors (n = 29), and subgroups of long-COVID patients with (n = 26) and without (n = 35) cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p < 0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNγ, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment. We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.

SARS-CoV-2 antibody levels and long COVID occurrence in blood donors.

BACKGROUND: Long COVID is a common condition lacking consensus definition; determinants remain incompletely understood. Characterizing immune profiles associated with long COVID could support the development of preventive and therapeutic strategies. METHODS: We used a survey to investigate blood donors' infection/vaccination history and acute/persistent symptoms following COVID-19. The prevalence of long COVID was evaluated using self-report and an adapted definition from the RECOVER study. We evaluated factors associated with long COVID, focusing on anti-spike and anti-nucleocapsid SARS-CoV-2 antibodies. Lastly, we investigated long COVID clinical subphenotypes using hierarchical clustering. RESULTS: Of 33,610 participants, 16,003 (48%) reported having had COVID-19; 1853 (12%) had self-reported long COVID, 685 (4%) met an adapted RECOVER definition, and 2050 (13%) met at least one definition. Higher anti-nucleocapsid levels measured 12-24 weeks post-infection were associated with higher risk of self-reported and RECOVER long COVID. Higher anti-spike IgG levels measured 12-24 weeks post-infection were associated with lower risk of self-reported long COVID. Higher total anti-spike measured 24-48 weeks post-infection was associated with lower risk of RECOVER long COVID. Cluster analysis identified four clinical subphenotypes; patterns included neurological and psychiatric for cluster 1; neurological and respiratory for cluster 2; multi-systemic for cluster 3; and neurological for cluster 4. DISCUSSION: Long COVID prevalence in blood donors varies depending on the adopted definition. Anti-SARS-CoV-2 antibodies were time-dependently associated with long COVID; higher anti-nucleocapsid levels were associated with higher risk; and higher anti-spike levels were associated with lower risk of long COVID. Different underlying pathophysiologic mechanisms may be associated with distinct clinical subphenotypes.

DYNamic Assessment of Multi-Organ level dysfunction in patients recovering from COVID-19: DYNAMO COVID-19.

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5-7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497-27,448) mIU/min/L] versus controls [8655 (7948-11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.

Long-term effects of COVID-19 on endothelial function, arterial stiffness, and blood pressure in college students: a pre-post-controlled study.

BACKGROUND: The COVID-19 has been shown to have negative effects on the cardiovascular system, but it is unclear how long these effects last in college students. This study aimed to assess the long-term impact of COVID-19 on arterial stiffness, endothelial function, and blood pressure in college students. METHODS: We enrolled 37 college students who had been infected with COVID-19 for more than 2 months. Brachial artery flow-mediated dilation (FMD) was used to assess endothelial function, while arterial stiffness was evaluated using the ABI Systems 100, including variables such as ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), carotid-femoral pulse wave velocity (cfPWV), heart rate (HR), and blood pressure (BP). RESULTS: Our results showed that FMD was significantly impaired after COVID-19 infection (p < 0.001), while cfPWV and systolic blood pressure (SBP) were significantly increased (p < 0.05). Simple linear regression models revealed a significant negative correlation between post-COVID-19 measurement time and baPWV change (p < 0.01), indicating an improvement in arterial stiffness over time. However, there was a significant positive correlation between post-COVID-19 measurement time and diastolic blood pressure (DBP) change (p < 0.05), suggesting an increase in BP over time. There were no significant differences in ABI and HR between pre- and post-COVID-19 measurements, and no significant correlations were observed with other variables (p > 0.05). CONCLUSION: Our study demonstrated that COVID-19 has long-term detrimental effects on vascular function in college students. However, arterial stiffness tends to improve over time, while BP may exhibit the opposite trend.

Incidence and risk factors of post COVID-19 syndrome: a Tunisian cohort study.

BACKGROUND: It has become increasingly clear that SARS-CoV-2 infection can lead to persistent physical and mental health problems lasting weeks or months, requiring prolonged periods of clinical care and increasing the burden on the healthcare system. This phenomenon, known as post COVID-19 syndrome (PCS), is a relatively new condition, its incidence is still unclear and differs between studies. OBJECTIVES: In this cohort study, we aimed to estimate the incidence of PCS and to identify its risk factors in the Tunisian population. METHODS: This is a prospective cohort study that enrolled patients diagnosed with COVID-19 from the triage unit of the University Hospital of Monastir, Tunisia. between April 2021 and June 2022. Patients were contacted by phone for a follow-up evaluation of PCS 12- weeks after the diagnosis date. RESULTS: A total of 1451 individuals diagnosed with COVID-19 during the study period, responded to the follow-up evaluation after 3 months. The incidence of PCS was found to be 44.03% (95% CI [41.47; 46.58]), with fatigue being the most common symptom (21.5%), followed by cognitive impairment (10.3%), including memory loss and difficulty concentrating. Multivariate analysis revealed that the main associated factors to PCS were female gender (RR = 1.54; CI95% [1.30 - 1.82]), pre-existing comorbidities (RR = 1.30; CI95% [1.10 - 1.52]), duration of acute COVID-19 illness (days) (RR = 1.02; CI95% [1.01 - 1.03]), hospitalization (RR = 1.27; CI95% [1.05 - 1.53]), number of COVID-19 episodes (RR = 1.46; CI 95% [1.28 - 1.67]) and patients having receive two or more doses of vaccine prior to COVID-19 infection (RR = 0.82; CI95% [0.70 - 0.96]). CONCLUSION: Our study allowed to estimate the incidence and identify risk factors of PCS. Recognizing these factors could help to better understand the underlying mechanisms and guide interventions for prevention and management of this condition.

Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions.

BACKGROUND: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC). METHODS: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10. RESULTS: Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals. CONCLUSIONS: This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.

Prolonged Fatigue and Mental Health Challenges in Critical COVID-19 Survivors.

Background: The aim of this study was to investigate the development of fatigue and mental illness between 3 and 12 months after critical COVID-19 and explore risk factors for long-lasting symptoms. Study Design and Methods: A prospective, multicenter COVID-19 study in southern Sweden, including adult patients (≥18 years) with rtPCR-confirmed COVID-19 requiring intensive care. Survivors were invited to a follow-up at 3 and 12 months, where patient-reported symptoms were assessed using the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS) and the Posttraumatic Stress Disorder Checklist version 5 (PCL-5). The development between 3 and 12 months was described by changes in relation to statistical significance and suggested values for a minimally important difference (MID). Potential risk factors for long-lasting symptoms were analyzed by multivariable logistic regression. Results: At the 3-month follow-up, 262 survivors (87%) participated, 215 (72%) returned at 12 months. Fatigue was reported by 50% versus 40%, with a significant improvement at 12 months (MFIS; median 38 vs. 33, P < .001, MID ≥4). There were no significant differences in symptoms of mental illness between 3 and 12 months, with anxiety present in 33% versus 28%, depression in 30% versus 22%, and posttraumatic stress disorder in 17% versus 13%. A worse functional outcome and less sleep compared to before COVID-19 were risk factors for fatigue and mental illness at 12 months. Conclusions: Fatigue improved between 3 and 12 months but was still common. Symptoms of mental illness remained unchanged with anxiety being the most reported. A worse functional outcome and less sleep compared to before COVID-19 were identified as risk factors for reporting long-lasting symptoms.

Anxiety and depression symptoms among patients with long COVID: a retrospective cohort study.

Patients suffering from post-acute sequelae of COVID-19 (PASC) have a higher prevalence of anxiety and depression than the general population. The long-term trajectory of these sequelae is still unfolding. To assess the burden of anxiety and depression among patients presenting to the University of Iowa Hospitals and Clinics (UIHC) post-COVID-19 clinic, we analyzed how patient factors influenced Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scores. In this retrospective cohort study, the GAD-7 and PHQ-9 questionnaire scores of patients presenting to the UIHC post-COVID clinic between March 2021-February 2022 (N = 455) were compared to the scores of a sample of patients presenting to the general internal medicine (GIM) clinic during the same period (N = 94). Our analysis showed that patients with an absent history of depression on their electronic medical record (EMR) problem list scored significantly higher on the GAD-7 (mean difference -1.62, 95% CI -3.12 to -0.12, p = 0.034) and PHQ-9 (mean difference -4.45, 95% CI -5.53 to -3.37, p < 0.001) questionnaires compared to their similar counterparts in the GIM clinic. On the other hand, patients with an absent history of anxiety on their EMR problem list scored significantly higher on the GAD-7 (mean difference -2.90, 95% CI -4.0 to -1.80, p < 0.001) but not on the PHQ-9 questionnaire (p = 0.196). Overall, patients with PASC may have experienced a heavier burden of newly manifest anxiety and depression symptoms compared to patients seen in the GIM clinic. This suggests that the mental health impacts of PASC may be more pronounced in patients with no prior history of anxiety or depression.

The lingering symptoms of post-COVID-19 condition (long-COVID): a prospective cohort study.

BACKGROUND: Longer-term symptoms (long COVID) may be present in seemingly recovered patients for several months and can be debilitating. AIM: To investigate the prevalence and type of symptoms in those with a prior COVID-19 diagnosis. METHODS: This prospective, longitudinal observational study commenced in July 2020 investigating the longer-term health impacts of COVID-19. Participants were recruited via public health units and media publicity. Surveys were completed upon enrolment, and at 1, 3, 6 and 12 months. Outcome measures included incidence of activity limitations and symptoms against health and vaccination status, age and gender. RESULTS: Overall, 339 participants were recruited. At 3 months after COVID-19, 66.8% reported symptoms, and 44.8% were still experiencing symptoms at 12 months. Fatigue was most common at every point (between 53.1% and 33.1%). Pain symptoms increased in relative prevalence over time, whereas respiratory/pulmonary-type symptoms decreased substantially after 3 months. Females and younger people were more likely to experience symptoms in the early stages of long COVID (P < 0.01) and those with more comorbidities in the latter stages (P < 0.001). Vaccination showed a statistically significant protective effect against symptoms (P < 0.01-0.001). CONCLUSION: Long-term COVID-19 symptoms exist among recovered patients up to 12 months after contracting the virus. Fatigue is a primary contributor, while chronic pain became more problematic after 6 months. Vaccination was a factor in preventing long-term symptoms and aiding faster recovery from symptoms. Further work exploring additional contributors to symptom prevalence would assist in developing appropriate follow-up care.

Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients.

BACKGROUND: COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR's effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals. METHODS: We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network's electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR. RESULTS: The 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR. CONCLUSION: Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients' functional status should be investigated in the future.

Long COVID-19 gastrointestinal related disorders and traditional Chinese medicine: A network target-based approach.

The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach.

Navigating an unfamiliar world - Parents' experiences of having a child with post COVID-19.

BACKGROUND: Post COVID-19 diagnosis in children has been difficult as there has been a lack of knowledge within the healthcare system, leading to uncertainty concerning how these children should be assessed and treated. To understand the aspects of how parents experience seeking care for their child with an array of symptoms and how the child's symptoms affect their everyday life and family situation, we need to listen to the parents' stories about having a child living with post COVID-19. PURPOSE: To describe parents' experiences of seeking professional care for their child with post COVID-19 symptoms and what kinds of impacts there are on their children's daily life. DESIGN AND METHODS: A qualitative study with an inductive and exploratory approach including seventeen parents of children with post COVID-19. Face-to-face interviews were conducted between October 2022 and March 2023 and analyzed with thematic analysis. RESULTS: The findings describe how the parents' constant struggle for their child and how the child's symptoms affect their daily life and their family situation in three themes: Navigating the unknown, Navigating life with post COVID-19, and Navigating between fear and hope for an uncertain future. CONCLUSIONS: This study corroborates the parents' struggle for acceptance of the children's problems in the health system. PRACTICE IMPLICATIONS: It is important that health care focuses on the everyday world and the problems that the child and parents express to understand the family's perspective and the problems that arise in everyday life.

Gut Microbiome Composition and Dynamics in Hospitalized COVID-19 Patients and Patients with Post-Acute COVID-19 Syndrome.

The gut microbiome plays a pivotal role in the modulation of host responses during viral infections, and recent studies have underscored its significance in the context of coronavirus disease 2019 (COVID-19). We aimed to investigate the dynamics and compositional changes in the gut microbiome of COVID-19 patients, addressing both the acute phase and the recovery process, with a particular focus on the emergence of post-COVID-19 conditions. Involving 146 COVID-19 patients and 110 healthy controls, this study employed a shotgun metagenomics approach for cross-sectional and longitudinal analyses with one- and three-month follow-ups. We observed a decline in taxonomic diversity among hospitalized COVID-19 patients compared to healthy controls, while a subsequent increase in alpha diversity was shown during the recovery process. A notable contribution of Enterococcus faecium was identified in the acute phase of the infection, accompanied by an increasing abundance of butyrate-producing bacteria (e.g., Roseburia, Lachnospiraceae_unclassified) during the recovery period. We highlighted a protective role of the Prevotella genus in the long-term recovery process and suggested a potential significance of population-specificity in the early gut microbiome markers of post-acute COVID-19 syndrome. Our study represents distinctive gut microbiome signatures in COVID-19, with potential diagnostic and prognostic implications, pinpointing potential modulators of the disease progression.

Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors.

PURPOSE: To analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospitalization. MATERIALS AND METHODS: In this prospective cohort study, patients were evaluated six months after hospitalization due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. RESULTS: Of 255 participants, 54.1% were men and the median age was 57.3 [44.3 - 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). One hundred and twenty-four patients (48.6%) had a hospital stay >15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS was 6 [3-11] and did not differ between genders. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Diabetes, hypertension, and self-perception of worse general health were associated with LUTS. CONCLUSIONS: LUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.

[Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen].

Рost-COVID-19 syndrome (PS) is one of the medical and social problem. According to WHO, 10-20% of COVID-19 patients suffer from PS. The use of medical gases - inhaled nitric oxide (iNO) and molecular hydrogen (iH2) - may influence on the mechanisms of development PC. AIM: To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. MATERIALS AND METHODS: 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H2<4% in the gas mixture), the control group (n=17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). RESULTS: The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p<0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p<0.001), and the date in oxidative damage (p<0.001) and antioxidant activity (p=0.03) parameters in the blood serum. CONCLUSION: The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes.

A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.